MYCN-driven fatty acid uptake is a metabolic vulnerability in neuroblastoma

Ling Tao, Mahmoud A. Mohammad, Giorgio Milazzo, Myrthala Moreno-Smith, Tajhal D. Patel, Barry Zorman, Andrew Badachhape, Blanca E. Hernandez, Amber B. Wolf, Zihua Zeng, Jennifer H. Foster, Sara Aloisi, Pavel Sumazin, Youli Zu, John Hicks, Ketan B. Ghaghada, Nagireddy Putluri, Giovanni Perini, Cristian Coarfa, Eveline Barbieri

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and pharmacological SLC27A2 inhibition selectively suppresses tumor growth, prolongs animal survival, and exerts synergistic anti-tumor effects when combined with conventional chemotherapies in multiple preclinical NB models. This study identifies FA uptake as a critical metabolic dependency for MYCN-amplified tumors. Inhibiting FA uptake is an effective approach for improving current treatment regimens.

Original languageEnglish (US)
Article number3728
Pages (from-to)3728
JournalNature Communications
Issue number1
StatePublished - Jun 28 2022


  • Animals
  • Cell Line, Tumor
  • Fatty Acids
  • N-Myc Proto-Oncogene Protein/genetics
  • Neuroblastoma/metabolism

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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